Development and validation of novel stability-indicating RP-HPLC method for estimation of related substances and degradation products in ambrisentan

Author(s): J.Sreenivasulu, CH.V.S.Nagaraju, S.Thirumalai Rajan, S.Eswaraiah, P.Venkata Ramana

Asimple, specific, precise, linear, accurate, reproducible and stability indicating RP-HPLCmethodwas developed for the quantative determination of related subatances and degradation products of Ambrisentan. The chromatographic separation was achieved by using Waters symmetry C18 column. The drug substance was subjected to stress conditions of hydrolysis (acid, base andwater), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating power of the method. Significant degradation was observed during acid, base and water hydrolysis studies. The mass balance ofAmbrisentan was close to 100% in all the stress condition. In the developed HPLC method, the resolution between Ambrisentan and its process-related impurities was found to be greater than 5.0. The limit of detection (LOD) was in the range of 13.6 to 31.2 ng/mL and limit of quantification (LOQ) found to be in the range of 58.4 ng/mL to105.6 ng/mL for Ambrisentan and their impurities. The method was validated for accuracy, linearity, precision, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines.

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